So essentially you have a base system and you add what you need through flatpak, distrobox, homebrew, and if all else fails, by layering the packages on the base image with rpm-ostree. What you can't do (that I'm aware of), is remove packages, or make bigger changes like adding another desktop environment aside what it came from. I mean, I guess you can do it by layering but it's probably messy.
Configuration and customisation are not an issue: /etc and /var are not immutable of course.

Distrobox is super cool btw, I knew it existed but Bazzite pushing me to use it was what I needed to finally try and appreciate it.